{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:53:45Z","timestamp":1788386025742,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T00:00:00Z","timestamp":1653091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novelgen Company","award":["S-2018-1158-000"],"award-info":[{"award-number":["S-2018-1158-000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Emerging Oseltamivir-resistant influenza strains pose a critical public health threat due to antigenic shifts and drifts. We report an innovative strategy for controlling influenza A infections by use of a novel minibody of the 3D8 single chain variable fragment (scFv) showing intrinsic viral RNA hydrolyzing activity, cell penetration activity, and epidermal cell penetration ability. In this study, we examined 3D8 scFv\u2019s antiviral activity in vitro on three different H1N1 influenza strains, one Oseltamivir-resistant (A\/Korea\/2785\/2009pdm) strain, and two Oseltamivir-sensitive (A\/PuertoRico\/8\/1934 and A\/X-31) strains. Interestingly, the 3D8 scFv directly digested viral RNAs in the ribonucleoprotein complex. scFv\u2019s reduction of influenza viral RNA including viral genomic RNA, complementary RNA, and messenger RNA during influenza A infection cycles indicated that this minibody targets all types of viral RNAs during the early, intermediate, and late stages of the virus\u2019s life cycle. Moreover, we further addressed the antiviral effects of 3D8 scFv to investigate in vivo clinical outcomes of influenza-infected mice. Using both prophylactic and therapeutic treatments of intranasal administered 3D8 scFv, we found that Oseltamivir-resistant H1N1-infected mice showed 90% (prophylactic effects) and 40% (therapeutic effects) increased survival rates, respectively, compared to the control group. The pathological signs of influenza A in the lung tissues, and quantitative analyses of the virus proliferations supported the antiviral activity of the 3D8 single chain variable fragment. Taken together, these results demonstrate that 3D8 scFv has antiviral therapeutic potentials against a wide range of influenza A viruses via the direct viral RNA hydrolyzing activity.<\/jats:p>","DOI":"10.3390\/v14051105","type":"journal-article","created":{"date-parts":[[2022,5,21]],"date-time":"2022-05-21T09:18:08Z","timestamp":1653124688000},"page":"1105","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Therapeutically Active Minibody Exhibits an Antiviral Activity in Oseltamivir-Resistant Influenza-Infected Mice via Direct Hydrolysis of Viral RNAs"],"prefix":"10.3390","volume":"14","author":[{"given":"Yongjun","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4343-7475","authenticated-orcid":false,"given":"Phuong","family":"Hoang","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongjun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramadhani","family":"Ayun","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quynh","family":"Luong","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungho","family":"Na","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taehyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Novelgen Co., Ltd., R&D Center, 77, Changnyong-daero 256 Beon-gil, Yeongtong-gu, Suwon 16229, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5743-5396","authenticated-orcid":false,"given":"Yeonsu","family":"Oh","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine and Institute of Veterinary Science, Kangwon National University, Chuncheon 24341, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Keun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology, College of Medicine, Hallym University, Chuncheon 24252, Korea"},{"name":"Institute of Medical Science, College of Medicine, Hallym University, Chuncheon 24252, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sukchan","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,21]]},"reference":[{"key":"ref_1","first-page":"603","article-title":"Emerging, novel, and known influenza virus infections in humans","volume":"24","author":"Tang","year":"2010","journal-title":"Infect. 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